Although the prototypical cigarette smoker is characterized as someone who consistently smokes a pack of cigarettes or more each day, a large number of people described as current smokers neither smoke daily nor consume a pack of cigarettes on days they do smoke. These low-level smokers incur increased health risk as a consequence of their inhalation of smoke. Moreover, for many, low-level smoking represents an important transition period for the development of nicotine dependence, the process presumably responsible for the intractability of cigarette smoking in heavy, chronic smokers. Because of the serious health consequences of low-level smoking and the important role of low-level smoking in emergence of nicotine dependence, it is important to conduct systematic research on this phenomenon. Research on low-level smoking is hampered by the relative absence of self-report instruments that can create an accurate profile of low-level smoking over time. Under ideal circumstances, the accuracy of self-report smoking measures would be validated by biological assays of nicotine exposure. Unfortunately, most conventional biomarker assays are sensitive only to relatively recent smoking and are not particularly useful in accurately characterizing low-levels of smoking. The research in this proposal is designed to validate the systematic use of biomarkers, hair nicotine and cotinine levels, as an accurate index of known low-level nicotine exposure. The research will also comparatively evaluate measures of self-report smoking with the intent of identifying measures that are maximally sensitive to variations in low-level smoking. The developed biomarkers will then be used to validate these self-report measures of smoking behavior. This research will integrate state-of-the-art pharmacology, analytical chemistry, and behavioral science in the development of new tools for the assessment of low-level cigarette smoking. This interdisciplinary approach offers the opportunity to simultaneously validate biological and behavioral indices of low-level smoking. Finally, this research will provide new tools, biological and behavioral, with considerable utility for our understanding of the impact of low-level smoking on health and on the development of nicotine dependence.